Transdermal delivery systems (adhesive patches) as dosage forms have been the subject of a vast number of patent applications over the last 25 years, yielding many patents but few commercial products in comparison. To those working in the field, the relatively small number of commercial products is not surprising. Although regulatory, economic, and market hurdles play a role in limiting the number of products on the market, the task of developing a transdermal delivery system that achieves desired physical and pharmacokinetic parameters to satisfy physician and patient demand is more daunting. Parameters to be considered during commercial product development may include drug solubility, drug stability (e.g., as may arise from interaction with other component materials and/or the environment), delivery of a therapeutic amount of drug at a desired delivery rate over the intended duration of use, adequate adhesion at the anatomical site of application, integrity (e.g., minimal curling, wrinkling, delaminating and slippage) with minimal discomfort, irritation and sensitization both during use and during and after removal, and minimal residual adhesive (or other components) after removal. Size also may be important from a manufacturing and patient viewpoint, and appearance may be important from a patient viewpoint. These factors become even more complicated when more than one drug is being formulated.
This invention relates generally to transdermal drug delivery systems, and more particularly, to transdermal drug delivery systems for the delivery of levonorgestrel and ethinyl estradiol.
U.S. Pat. No. 7,045,145 is directed to a transdermal delivery system comprising a backing layer, and an adhesive polymer matrix affixed to the backing layer, wherein the adhesive polymer matrix is formulated by combining, on a weight percentage basis: (a) from about 0% to about 10% of a humectant/plasticizer; (b) from about 20% to about 70% of an adhesive copolymer; (c) from about 10% to about 60% percent of a combination of skin permeation enhancing agents which is a mixture comprising dimethyl sulfoxide, a fatty (C8-C20) alcohol ester of lactic acid, a lower (C1-C4) alkyl ester of lactic acid and capric acid present in ratio ranging from about 2:1:1:0.8 to about 6:1:1:0.8, respectively; (d) a progestin hormone; and (e) an estrogen hormone.
U.S. Pat. No. 7,384,650 is directed to a transdermal hormone delivery system comprising a backing layer and an adhesive polymer matrix affixed to the backing layer, wherein the adhesive polymer matrix comprises: (a) an adhesive polymer; (b) a humectant; (c) a combination of skin permeation enhancing agents consisting essentially of, on a final percentage by weight of the adhesive polymer matrix after fabrication of the system, from about 4% to about 12% dimethyl sulfoxide; from about 4.2% to about 12.6% a fatty (C8-C20) alcohol ester of lactic acid; from about 0.7% to about 2.3% lower (C1-C4) alkyl ester of lactic acid; and from about 3% to about 9% capric acid; (d) a progestin; and (e) an estrogen.
U.S. Pat. No. 8,221,785 is directed to a contraceptive delivery system comprising a backing layer and an adhesive polymer matrix affixed to the backing layer, wherein the adhesive polymer matrix comprises: (a) an adhesive polymer comprising a polyacrylate copolymer; (b) a humectant comprising polyvinylpyrrolidone; (c) a combination of skin permeation enhancing agents consisting essentially of, on a final percentage by weight of the adhesive polymer matrix after fabrication of the system, from about 4% to about 12% dimethyl sulfoxide; from about 4.2% to about 12.6% a fatty (C8-C20) alcohol ester of lactic acid; from about 0.7% to about 2.3% lower (C1-C4) alkyl ester of lactic acid; and from about 3% to about 9% capric acid; (d) levonorgestrel; and (e) ethinyl estradiol or 17 beta-estradiol.
U.S. Pat. No. 5,770,219 is directed to a drug-containing matrix for use in a transdermal drug delivery device for administering at least one estrogen to an area of skin or mucosa comprising the estrogen dispersed in a body of a pressure sensitive adhesive, said pressure-sensitive adhesive comprising an acetate acrylate copolymer and polyvinylpyrrolidone, said matrix being essentially free of a skin permeation enhancer. In some embodiments, the matrix further comprises levonorgestrel.
Nevertheless, the transdermal delivery of levonorgestrel and ethinyl estradiol continues to present challenges, and currently there is no commercial transdermal combination product on the market. Some of the challenges presented by this particular drug combination include the high delivery rate of levonorgestrel and its impact on patch size; the undesired crystallization of levonorgestrel in the polymer matrix; and the difficulty of formulating a composition that can achieve sustained drug delivery (e.g., at therapeutic levels) over a period of time of 7 days.
Thus, there remains a need for transdermal drug delivery systems designed for the delivery of specific drugs and drug combinations, such as levonorgestrel and ethinyl estradiol.